(1) Metabolism is the link between myocardial blood flow and physiological performance of the heart. (2) Metabolic myocardial radiopharmaceuticals have the potential to identify metabolic alterations unique to a given intrinsic cardiac disease (e.g. cardiomyopathies), to assess acute metabolic changes or in delineating a specific chronic metabolic defect (e.g. coronary artery disease). (3) Two approaches can be employed to evaluate in vivo myocardial utilization of subtracts: (a) use of radiolabeled "physiologic" substrates e.g. positron emitting 11C-palmitic acid was successfully employed for assessing the in vivo metabolic sequelae of myocardial ischemia, infarction and cardiomyopathies, and (b) use of modified tracers which enter known metabolic pathways. However, because of their unique structure, metabolism of the tracer stops at a certain state thus leaving the radiolabel trapped in the cell, e.g. [18F]FDG for measuring glucose metabolic rate in the human brain and myocardium. (4) Among the radiopharmaceuticals for planar and single photon tomography, the para and the ortho isomers of 123I-phenyl iodoheptadecanoic acids and their beta-methyl derivatives are the most promising tracers for myocardial metabolic studies. (5) Ortho-(123I-phenyl)-pentadecanoic acid (o-IPPA) human myocardial uptake was rapidly and markedly elevated in well perfused segments; myocardial turnover was strikingly prolonged, suggesting some "trapping" phenomenon, resulting in excellent scintigrams. This is in contrast to the relatively shorter clearance of the para isomer from the myocardium. (6) 11C-Palmitic acid and [18F]FDG are the most widely used for PET scanning for following myocardial metabolism. The most important clinical application of these agents is predicting viability of ischemic myocardium. (7) A significant proportion of fixed perfusion defects seen on thallium studies can be demonstrated to be viable myocardium on PET scans using metabolic agents. If the markers of perfusion alone are relied on to assess tissue viability, the extent of salvageable myocardium may be underestimated. The demonstration of myocardial viability is crucial in the decision of the optimal treatment of the disease.